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Kevin kain Andrea conroy

Andrea L Conroy, Michael Hawkes, Chloe R McDonald, Hani Kim, Sarah J Higgins, Kevin R Barker, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
Background.  Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions. Methods.  This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria...
September 2016: Open Forum Infectious Diseases
Sarah J Higgins, Lisa A Purcell, Karlee L Silver, Vanessa Tran, Valerie Crowley, Michael Hawkes, Andrea L Conroy, Robert O Opoka, John G Hay, Susan E Quaggin, Gavin Thurston, W Conrad Liles, Kevin C Kain
Cerebral malaria is a leading cause of global morbidity and mortality. Interventions targeting the underlying pathophysiology of cerebral malaria may improve outcomes compared to treatment with antimalarials alone. Microvascular leak plays an important role in the pathogenesis of cerebral malaria. The angiopoietin (Ang)-Tie-2 system is a critical regulator of vascular function. We show that Ang-1 expression and soluble Tie-2 expression were associated with disease severity and outcome in a prospective study of Ugandan children with severe malaria and in a preclinical murine model of experimental cerebral malaria...
September 28, 2016: Science Translational Medicine
Robyn E Elphinstone, Andrea L Conroy, Michael Hawkes, Laura Hermann, Sophie Namasopo, H Shaw Warren, Chandy C John, W Conrad Liles, Kevin C Kain
BACKGROUND: Malaria remains a major cause of global mortality. Extracellular heme, released during malaria-induced hemolysis, mediates a number of pathogenic processes associated with vascular and organ injury. Hemopexin (hpx) facilitates the degradation of extracellular heme. In this study, we explore the hypothesis that dysregulation of the heme-hpx axis is associated with disease severity, acute kidney injury (AKI), and outcome. METHODS: Plasma levels of hemin and hpx (at admission, day 3, and day 14) were assessed in children with severe malaria in Jinja, Uganda...
October 15, 2016: Journal of Infectious Diseases
Andrea L Conroy, Michael Hawkes, Robyn E Elphinstone, Catherine Morgan, Laura Hermann, Kevin R Barker, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
Background.  Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods.  One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay...
March 2016: Open Forum Infectious Diseases
Kevin R Barker, Andrea L Conroy, Michael Hawkes, Holly Murphy, Prativa Pandey, Kevin C Kain
BACKGROUND: The mechanisms underlying acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) are not fully understood. We hypothesized that regulators of endothelial function, circulatory homeostasis, hypoxia and cell stress contribute to the pathobiology of AMS and HAPE. METHODS: We conducted a prospective case-control study of climbers developing altitude illness who were evacuated to the CIWEC clinic in Kathmandu, compared to healthy acclimatized climbers...
March 2016: Journal of Travel Medicine
Susan M Graham, Junmei Chen, Dominic W Chung, Kevin R Barker, Andrea L Conroy, Michael T Hawkes, Sophie Namasopo, Kevin C Kain, José A López, W Conrad Liles
BACKGROUND: Malaria is a major cause of morbidity and mortality in sub-Saharan Africa, and poor outcomes have been associated with endothelial activation. In this study, biomarkers of endothelial activation, haemostasis, and thrombosis were measured in Ugandan children with severe malaria who participated in a clinical trial, in order to investigate associations between these processes. METHODS: Serum and plasma were collected from participants at baseline (day 1), and on days 2, 3, 4, and 14...
2016: Malaria Journal
Michael T Hawkes, Andrea L Conroy, Robert O Opoka, Laura Hermann, Kevin E Thorpe, Chloe McDonald, Hani Kim, Sarah Higgins, Sophie Namasopo, Chandy John, Chris Miller, W Conrad Liles, Kevin C Kain
BACKGROUND: Severe malaria remains a major cause of childhood mortality globally. Decreased endothelial nitric oxide is associated with severe and fatal malaria. The hypothesis was that adjunctive inhaled nitric oxide (iNO) would improve outcomes in African children with severe malaria. METHODS: A randomized, blinded, placebo-controlled trial of iNO at 80 ppm by non-rebreather mask versus room air placebo as adjunctive treatment to artesunate in children with severe malaria was conducted...
October 29, 2015: Malaria Journal
Andrea L Conroy, Margarita Gélvez, Michael Hawkes, Nimerta Rajwans, Vanessa Tran, W Conrad Liles, Luis Angel Villar-Centeno, Kevin C Kain
OBJECTIVES: Dengue represents the most important arboviral infection worldwide. Onset of circulatory collapse can be unpredictable. Biomarkers that can identify individuals at risk of plasma leakage may facilitate better triage and clinical management. DESIGN: Using a nested case-control design, we randomly selected subjects from a prospective cohort study of dengue in Colombia (n=1582). Using serum collected within 96 hours of fever onset, we tested 19 biomarkers by ELISA in cases (developed dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS); n=46), and controls (uncomplicated dengue fever (DF); n=65) and healthy controls (HC); n=15...
November 2015: International Journal of Infectious Diseases: IJID
Chloe R McDonald, Anne M Darling, Andrea L Conroy, Vanessa Tran, Ana Cabrera, W Conrad Liles, Molin Wang, Said Aboud, Willy Urassa, Wafaie W Fawzi, Kevin C Kain
RESEARCH QUESTION: Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB). STUDY DESIGN: Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12-27 weeks gestation...
2015: PloS One
Saleh Nyende, Andrea Conroy, Robert Opika Opoka, Sophie Namasopo, Kevin C Kain, Arthur Mpimbaza, Ravi Bhargava, Michael Hawkes
BACKGROUND: Pneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves survival in children with pneumonia, yet its availability remains limited in many resource-constrained settings where most deaths occur. Solar-powered oxygen delivery could be a sustainable method to improve oxygen delivery in remote areas with restricted access to a supply chain of compressed oxygen cylinders and reliable electrical power. METHODS/DESIGN: This study is a randomized controlled trial (RCT)...
2015: Trials
Michael Hawkes, Andrea L Conroy, Robert O Opoka, Sophie Namasopo, Kathleen Zhong, W Conrad Liles, Chandy C John, Kevin C Kain
Plasmodium falciparum resistance to artemisinin derivatives is emerging in Asia. We examined molecular markers of resistance in 78 children in Uganda who had severe malaria and were treated with intravenous artesunate. We observed in the K13-propeller domain, A578S, a low-frequency (3/78), nonsynonymous, single-nucleotide polymorphism associated with prolonged parasite clearance.
July 2015: Emerging Infectious Diseases
Andrea L Conroy, Michael Hawkes, Kyla Hayford, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
INTRODUCTION: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally. METHODS: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA)...
2015: Critical Care: the Official Journal of the Critical Care Forum
Anne Marie Darling, Chloe R McDonald, Andrea L Conroy, Kyla T Hayford, W Conrad Liles, Molin Wang, Said Aboud, Willy S Urassa, Kevin C Kain, Wafaie W Fawzi
OBJECTIVE: We sought to investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in midpregnancy and small-for-gestational-age (SGA) outcomes in sub-Saharan Africa. STUDY DESIGN: Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania, who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birthweight for gestational age relative to the applied growth standards were considered SGA...
November 2014: American Journal of Obstetrics and Gynecology
Michael Hawkes, Andrea L Conroy, Robert O Opoka, Sophie Namasopo, W Conrad Liles, Chandy C John, Kevin C Kain
Severe malaria is frequently managed without access to laboratory testing. We report on the performance of point-of-care tests used to guide the management of a cohort of 179 children with severe malaria in a resource-limited Ugandan hospital. Correlation coefficients between paired measurements for glucose (i-STAT and One Touch Ultra), lactate (i-STAT and Lactate Scout), and hemoglobin (Hb; laboratory and i-STAT) were 0.86, 0.85, and 0.73, respectively. The OneTouch Ultra glucometer readings deviated systematically from the i-STAT values by +1...
April 2014: American Journal of Tropical Medicine and Hygiene
Michael Hawkes, Andrea L Conroy, Robert O Opoka, Sophie Namasopo, W Conrad Liles, Chandy C John, Kevin C Kain
BACKGROUND: Rapid diagnostic tests (RDTs) for malaria provide a practical alternative to light microscopy for malaria diagnosis in resource-limited settings. Three-band RDTs incorporating two parasite antigens may have enhanced diagnostic specificity, relative to two-band RDTs with a single parasite antigen (typically histidine-rich protein 2 [HRP2]). METHODS: Phase 1: 2,000 children, two months to five years of age, admitted to a referral hospital in Jinja, Uganda, with acute febrile illness were enrolled...
2014: Malaria Journal
Andrea L Conroy, Margarita Gélvez, Michael Hawkes, Nimerta Rajwans, W Conrad Liles, Luis Angel Villar-Centeno, Kevin C Kain
BACKGROUND: Dengue fever and leptospirosis have partially overlapping geographic distributions, similar clinical presentations and potentially life-threatening complications but require different treatments. Distinguishing between these cosmopolitan emerging pathogens represents a diagnostic dilemma of global importance. We hypothesized that perturbations in host biomarkers can differentiate between individuals with dengue fever and leptospirosis during the acute phase of illness. METHODS: We randomly selected subjects from a prospective cohort study of acute febrile illness in Bucaramanga, Colombia and tested 19 serum biomarkers by ELISA in dengue fever (DF, n = 113) compared to subjects with leptospirosis (n = 47)...
2014: BMC Infectious Diseases
Michael Hawkes, Robyn E Elphinstone, Andrea L Conroy, Kevin C Kain
Malaria affects millions of people around the world and a small subset of those infected develop cerebral malaria. The clinical presentation of cerebral malaria differs between children and adults, and it has been suggested that age-related changes in the endothelial response may account for some of these differences. During cerebral malaria, parasites sequester within the brain microvasculature but do not penetrate into the brain parenchyma and yet, the infection causes severe neurological symptoms. Endothelial dysfunction is thought to play an important role in mediating these adverse clinical outcomes...
August 15, 2013: Virulence
Andrea L Conroy, Karlee L Silver, Kathleen Zhong, Monique Rennie, Peter Ward, J Vidya Sarma, Malcolm E Molyneux, John Sled, Joseph F Fletcher, Stephen Rogerson, Kevin C Kain
Placental malaria (PM) is a major cause of fetal growth restriction, yet the underlying mechanism is unclear. Complement C5a and C5a receptor levels are increased with PM. C5a is implicated in fetal growth restriction in non-infection-based animal models. In a case-control study of 492 pregnant Malawian women, we find that elevated C5a levels are associated with an increased risk of delivering a small-for-gestational-age infant. C5a was significantly increased in PM and was negatively correlated with the angiogenic factor angiopoietin-1 and positively correlated with angiopoietin-2, soluble endoglin, and vascular endothelial growth factor...
February 13, 2013: Cell Host & Microbe
Andrea L Conroy, Chloe R McDonald, Kevin C Kain
Despite increased malaria control efforts, recent reports indicate that over 1.2 million deaths due to malaria occurred in 2010. Pregnant women represent a particularly vulnerable risk group as malaria infection can lead to life-threatening disease for the mother and fetus. With 125 million women at risk of malaria in pregnancy every year, better diagnostic tools are needed for timely identification and treatment of malaria infection. Diagnostic surveillance tools are also needed to estimate disease burden and inform public health policies...
November 2012: Expert Review of Anti-infective Therapy
Andrea L Conroy, Simon J Glover, Michael Hawkes, Laura K Erdman, Karl B Seydel, Terrie E Taylor, Malcolm E Molyneux, Kevin C Kain
OBJECTIVE: To investigate the relationship among the angiopoietin-Tie-2 system, retinopathy, and mortality in children with cerebral malaria. DESIGN: A case-control study of retinopathy-positive vs. retinopathy-negative children with clinically defined cerebral malaria. SETTING: Queen Elizabeth Central Hospital in Blantyre, Malawi. SUBJECTS: One hundred fifty-five children presenting with severe malaria and meeting a strict definition of clinical cerebral malaria (Blantyre Coma Score ≤ 2, Plasmodium falciparum parasitemia, no other identifiable cause for coma) were included in the study...
March 2012: Critical Care Medicine
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